Arsenic‐Induced Inflammatory Response via ROS‐Dependent Activation of ERK/NF‐kB Signaling Pathways: Protective Role of Natural Polyphenol Tannic Acid

Abstract

Arsenic (As), a highly toxic metalloid, is present throughout our environment as a result of both natural and human‐related activities. Furthermore, As exposure could lead to a persistent inflammatory response, which may facilitate the pathogenesis of several diseases in various organs. This study was performed to investigate the As‐induced inflammatory response and the underlying molecular mechanisms in vitro. Further, the anti‐inflammatory effects of a natural dietary polyphenol tannic acid (TA) were also explored. In human normal bronchial (BEAS‐2B), adenocarcinoma alveolar basal (A549), and murine macrophages (J774) cell lines, a trivalent form of As (as As3+) exposure markedly induced the expression of various pro‐inflammatory mediators (cytokines and chemokines). Additionally, it was found that As3+ exposure induced reactive oxygen species (ROS) generation and activation of the nuclear factor‐kappa B (NF‐kB) p65 and extracellular signal‐regulated kinase (ERK)1/2 pathways in BEAS‐2B cells. As expected, the blockade of either ERK1/2 (PD98059) or NF‐kB p65 (IMD0354), or both pathways attenuated As3+‐induced pro‐inflammatory mediators release. Interestingly, pre‐treatment with ROS inhibitor N‐acetylcysteine (NAC) attenuated activation of ERK/NF‐kB pathways, suggesting that ROS have a critical role in pathway's activation and subsequent inflammatory response. Further, TA pre‐treatment effectively attenuated As3+‐induced inflammatory response by suppressing ROS production and ERK/NF‐kB signaling pathways activation. Therefore, this study provides scientific evidence for the anti‐inflammatory activities of TA and the underlying molecular mechanisms.